Reagent bottle identification and reagent monitoring system for a chemical analyzer

ABSTRACT

An automatic chemical analyzer utilizes reagents supplied in reagent bottles. The reagent bottles are labeled on their bottom surfaces with an identification label bearing a machine-readable identification code. The automatic chemical analyzer includes a reagent tray having a plurality of tray apertures therein which receive coded reagent bottles and which expose the bottom surface of each bottle for optical viewing of the machine-readable identification code. The analyzer further includes optical scanner means positioned below the reagent tray for reading the machine-readable identification code on the bottom surfaces of reagent bottles within the tray apertures. The tray apertures are selectively located over the optical scanner means so that the analyzer can identify the reagent bottle and the contents thereof. 
     The identification label has a spaced pair of position reference dots defining and orienting a label area. A plurality of bit fields surround the position reference dots, their positions being defined by the position reference dots. Each bit field maps to a single bit of a multi-bit binary bottle identification code. Bit dots are printed in selected bit fields to define the binary value of each bit of the multi-bit binary identification code.

TECHNICAL FIELD

This disclosure pertains to a clinical chemistry analyzer for testing ofpatient samples, such as blood or urine. It generally relates toautomatic chemical analyzers for directly measuring properties ofreacted liquids by photometric systems. It specifically pertains to anidentification system for regent bottles used in conjunction with thetesting instrument, including machine-readable labels affixed to thebottles.

BACKGROUND OF INVENTION

Automated analyzers have been developed for biochemical analysis ofpatient samples such as whole blood, serum, urine, plasma and cerebralspinal fluid. Most such equipment available today is complicated tooperate, large in size and high in cost.

The operation of such equipment is technically complicated. It typicallyrequires specialized operators to be available at all times, withcommensurate personnel expenses being encountered. It is usuallydesigned for use by large laboratories serving a wide geographic area orby a large medical facility. These existing analyzers carry out tests ina defined sequence of operations designed for efficient, high volumeusage.

Such large scale capacity is not always required, particularly insmaller medical clinics where large volumes of blood samples are notencountered on a daily basis. The present chemical analyzer wasdeveloped to meet the practical needs of smaller medical settings. It isdesigned as a desk-top unit that can be operated without specializedlaboratory training. Its throughput is adequate for meeting typicalclinical applications. As an example, it can be designed to produce amaximum of 164 test results per hour for routine, single reagentchemistries. To provide a representative wide number of reagents, theanalyzer has been designed to have a capacity of 40 reagent containersof two different sizes on board. Its capacity can be effectively doubledby utilizing two of the chemistry instruments in tandem, both beingcontrolled by a common workstation.

The compact nature of the analyzer can be partially attributed to thefact that a single probe arm and pipette service all of the functionalliquid-handling components included within it. The common pipette isused for transferring samples and reagents, as well as for dilutingliquids as needed by particular test requirements.

To obtain large volumes of tests, conventional laboratory analyzers areprogrammed to conduct test procedures in a fixed sequence of events.While predetermined test sequences are practical in high volume chemicalanalyzer applications, there is a need for more flexible operation whenscaling such test procedures to meet the needs of smaller medicalfacilities.

The present invention provides testing flexibility by permitting randomaccess to each cuvette on a test turntable and to each container (cups,wells and reagent bottles) on a sample/reagent tray. It is therefore notnecessary for the instrument to sequence through any predeterminedprocessing steps--the controlling software can tailor the required stepsto the tests currently requisitioned. This permits a greater number oftests to be conducted while using a minimum number of containers,cuvettes and reagent bottles. The software controls the sequencing oftests based upon predetermined priority schedules, rather than definedtest sequences dictated by the nature of the tests being conducted.

The automated controls for the present chemical analyzer minimizeoperator training and required skill levels. Reagent bottles areautomatically read and identified by applied computer coded labels.Sample and reagent sensing that occurs automatically during operation ofthe analyzer notifies the operator of depleted liquid conditions as theyoccur.

Further details concerning the system will be evident from the followingdescription.

BRIEF DESCRIPTION OF THE DRAWINGS

The preferred embodiment of the invention is illustrated in theaccompanying drawings, in which:

FIG. 1 is a diagrammatic perspective view of the principal components inthe analyzer;

FIG. 2 is a perspective view of the analyzer;

FIG. 3 is a plan view of the chemical instrument enclosure;

FIG. 4 is a plan view of the chemical instrument enclosure with thecover removed;

FIG. 5 is a front elevation view of the enclosure;

FIG. 6 is a plan view of the assembled sample/reagent tray;

FIG. 7 is a sectional view taken along line 7--7 in FIG. 6;

FIG. 8 is a plan view of the reagent tray;

FIG. 9 is a side elevation view of a cup segment removed from the tray;

FIG. 10 is a plan view of the supporting platform well;

FIG. 11 is a bottom view of a labelled bottle;

FIG. 12 is a similar view, showing the label encoding pattern; and

FIG. 13 is a diagrammatic view of the label reading equipment in achemical instrument.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

This disclosure of the invention is submitted in furtherance of theconstitutional purposes of the U.S. Patent Laws "to promote the progressof science and useful arts" (Article 1, Section 8).

System Overview

The automatic chemical analyzer (generally illustrated in FIGS. 1-3)includes a turntable 11 rotatably mounted about a first vertical axis. Aplurality of disposable cuvettes 10 are releasably mounted to theturntable 11. A first power means, shown as motor 12, is operablyconnected to turntable 11 for alternately (1) indexing it at astationary angular position about the first ,axis with a selectedcuvette 10 positioned at a cuvette access station A or (2) turning itabout the first axis while mixing or centrifuging contents of cuvettesmounted to it.

First analytical means, illustrated as an optical system 14, is providedadjacent to the turntable 11 for performing tests on the contents of thecuvettes 10 as they rotate about the turntable axis.

A tray 15 is rotatably mounted about a second vertical axis parallel toand spaced from the first axis. A plurality of containers 25, 35, and 36are positioned about tray 15 for reception of samples and reagentliquids. Second power means, illustrated as motor 16, is operablyconnected to the tray 15. The motor 16 indexes tray 15 to a stationaryangular position about the second axis with a selected containerpositioned at a container access station C.

The analyzer also includes a probe arm 17 movable about a third verticalaxis parallel to the first axis. Probe arm 17 supports adownwardly-extending open pipette 18. The vertical pipette 18 is movablealong an arcuate path centered about the third axis and intersectingboth the cuvette access station A and container access station C. It canmove along the arcuate path in a random fashion to transfer liquid froma container positioned on the tray at the container access station C toa cuvette 10 positioned on the turntable 11 at the cuvette accessstation A. The arcuate path of the pipette 18 can be visualized along aprotective groove 29 formed at the exterior of the enclosure 39 housingthe chemistry instrument 24.

The illustrated embodiment of the clinical chemistry analyzer consistsof two major components: a chemistry instrument 24 and a workstation 30.The chemical instrument accepts liquid patient samples for testingpurposes, performs appropriate optical and/or potentiometricmeasurements on the samples, and communicates the resulting test data toworkstation 30. Workstation 30 is used by the operator to enter data,control operation of instrument components, accept data generated by theinstrument, manage and maintain system information, and generate visualand printed reports about assays and instrument performance.

The chemistry instrument 24 is a separate unit with minimal operatorcontrols. Either one or two identical chemistry instruments 24 can belinked to a single workstation 30, as required in a particular setting.The chemistry instrument 24 can perform several types of analysis. Theseinclude routine chemistries, electrolytes, therapeutic drug monitoring,drugs of abuse in urine, and other specialized tests.

The liquid-handling components that make up the chemistry instrument 24are housed within enclosure 39 (FIGS. 2-5). It separates along aperipheral parting line 37 defining a lower supporting base 33 and anupper hinged cover 34.

The principal modular components of the chemistry instrument 24 arediagrammatically illustrated in FIG. 1. The illustrated components arespecifically designed for use in association with a specially designedliquid cuvette 10.

A computerized operator interface to the chemistry instrument 24 isprovided through connections to the programmable workstation 30. Most ofthe operator interactions with the analyzer take place at workstation30. It is an external desktop computer located near the chemistryinstrument(s) 24. It uses an industry standard operating system and busstructure, plus a hard disk. It is also provided with a custominstrument interface board for each associated chemistry instrument.

Operations required for sample testing of cuvette contents are notcarried out in any predetermined sequence dictated by insertion of asample into the chemistry instrument 24. Instead, workstation 30 servesas random access control means operably connected to the turntable 11,tray 15 and probe arm 17 for selectively transferring liquid from anycontainer on the tray 15 to any cuvette 10 on the turntable 11 accordingto defined logical priority rules programmed into the workstation.

Operations carried out within the chemistry instrument 24 are timedabout a repetitious cycle of operations. Each cycle involvessequentially transferring liquids to an awaiting cuvette 10 on theturntable 11, mixing the liquids, and centrifuging them for testpurposes.

A monitor 31 is included within workstation 30 to display data, messagesand optional menus for the operator. A keyboard 32 is included foroperator input of data and instructions. A printer (not shown) ofconventional design can also be provided in the system to record testsresults and reports as required.

A plurality of test cuvettes 10 are releasably located within amotor-controlled turntable 11. It is powered by a DC motor 12. Motor 12can be accurately controlled to (1) selectively index turntable 11 at achosen angular position about its vertical axis for access to aparticular cuvette and/or insertion of new cuvettes or (2)intermittently or reversibly rotate turntable 11 about its axis formixing the contents of the cuvettes or (3) spin turntable 11 forcentrifuging the contents of the cuvettes during photometric analysis.

A liquid transfer module includes a single probe arm 17 movablysupported on the instrument 24 about a vertical axis. The outer end ofprobe arm 17 carries a downwardly extending pipette 18. Pipette 18 isused for transferring liquids between various locations about thechemistry instrument. Its lower or outer end is open for receiving ordischarging liquids.

Probe arm 17 is supported and powered by a positioning assembly 19. Thepositioning assembly 19 has two stepper motors--one for impartingrotational motion to probe arm 17 and one for imparting vertical motionto it. Positioning assembly 19 can selectively move probe arm 17 andpipette 18 both angularly and axially relative to the vertical axis ofprobe arm 17.

The tip or lower end of pipette 18, while in an elevated conditionpermitting angular movement about the chemistry instrument 24, projectsslightly into an open arcuate groove 29 (FIGS. 2, 3) formed about thecover 34 of the instrument enclosure. Groove 29 is centered about theaxis of probe arm 17 and is recessed within cover 34. It overlaps thebottom of pipette 18 to prevent its accidental engagement with the handsof an operator as the pipette travels from one station to the next. Theprotective overlap of the pipette tip eliminates the danger ofaccidently impaling adjacent personnel when pipette 18 is subsequentlylowered.

A cuvette dispenser module 13 is arranged on the framework of theequipment in a position immediately above the turntable 11. It includesa storage magazine for a plurality of stacks of cuvettes 10. It alsoincludes an apparatus for transferring individual cuvettes 10 from arandomly selectable stack within the magazine 75 to a receivingcompartment on turntable 11. Used cuvettes 10 are discarded into aremovable cuvette disposal container (not shown) as new cuvettes aredelivered to the turntable 11 by operation of a reciprocating ram. Thecuvette disposal container can be a bag or bin into which used cuvettesdrop when ejected from turntable 11.

The optical system 14 is contained within a housing positioned next toturntable 11. Optical system 14 performs photometric tests on thecontents of cuvettes 10 while they are being spun about the turntableaxis. The optical system 14 measures both fluorescent emissions andlight absorbance by cuvette contents within the turntable 11.Photometric test groups typically supported include routine chemistries,special proteins, therapeutic drugs, and drugs of abuse.

For absorbency tests, the optical system 14 measures radiation at 180degrees to the incident light. Readings are made at several wavelengthson a diode array, but only those points requested in specified testparameters are processed by the instrument 24. System offsets aresubtracted from the results and the sample signal is divided by areference signal. The negative logarithm of this ratio is theabsorbance.

When conducting fluorescent tests, emitted radiation at a wavelengthlonger than that of the source is measured at 90 degrees to the incidentbeam. System offsets are subtracted and the intensity is then normalizedusing a reference signal.

A sample/reagent tray 15 is rotatably mounted about a vertical axisparallel to and spaced from the axis of turntable 11. It is rotatablypowered by a stepper motor 16. Tray 15 consists of a circular reagentbottle support surrounded by separate interlocking ring segments 26. Theremovable ring segments 26 are used to hold reagents and samplesrequired for assay procedures during operation of chemistry instrument24.

Tray 15 supports a plurality of liquid containers, namely the reagentbottles 25, open cups 35 and open wells 36. The interchangeable ringsegments 26 have two alternate configurations. One includes aperturesfor removably supporting individual sample cups 35. The other includes aplurality of integrally molded sample wells 36.

The individually removable cups 35 serve as containers for test samplessupplied to the instrument 24 by the operator within one or more cupswithin a ring segment 26. Wells 36 are used by the instrument componentsin conjunction with operation of probe arm 17 for aliquoting of samplesfrom a draw tube and for sample dilution purposes. The probe arm 17 canselectively transfer liquids from one well 36 to a second well 36, froma cup 35 to a well 36, or from a reagent bottle 25 to a well 36.

Access to the sample/reagent tray 15 is provided by a hinged tray accesscover 8 formed in the enclosure cover 34. More limited manual access toa single ring segment 26 located at the front of the chemistryinstrument 24 is provided by a hinged segment access port 7, which is asub-assembly of cover 8.

A stepper motor 16 can be operated to index sample/reagent tray 15 to aselected position about its axis with one or more selected containers atone of four container access stations shown in FIG. 3 at locations C₁,C₂, C₃, C₄ on the equipment framework. Each container access stationintersects the path of pipette 18, which is coincident with groove 29.

Scanning means is provided next to the tray 15 for capturing identifyinginformation from encoded indicia on a container positioned on it.

A cooling system (not shown) for the chemistry instrument 24incorporates multiple thermoelectric cooling units. These are needed inthe areas of the sample/reagent tray 15 and the turntable 11. Heat canbe removed from the system by air exchange through a plurality of heatsinks.

A sample tube entry port 20 is provided on the framework for receivingand supporting successive individual draw tubes 27 as they areintroduced into the instrument by the operator. Its primary use is topermit the taking of aliquots from positively identified, sealed patientdraw tubes. It can also be used for delivery of control liquids fromtubes of a similar exterior configuration, whether covered or open.Positive identification can be provided by an encoded label on each drawtube 27. The label is scanned by a bar code reader included within thesample tube entry port 20.

Each draw tube 27, of conventional design, is sealed by a closure at itsupper end. Sample tube entry port 20 supports each manually inserteddraw tube 27 while pipette 18 pierces the closure 162 to access liquidsample material from the tube interior. Liquid removal from successivetubes 27 occurs at a sample access station B along the arcuate path 29.

Puncturing means are provided within the sample tube entry port 20 fortemporarily forming an opening through a closure on a manually-delivereddraw tube 27 placed within it. A ram positioned below the puncturingmeans receives and coaxially orients a manually placed draw tube 27relative to the puncturing means. It moves the draw tube parallel to afourth vertical axis (centered along the puncturing means) between alowered position wherein the draw tube 27 is clear of the puncturingmeans and a raised position wherein the puncturing means forms atemporary opening through the draw tube closure for subsequent coaxialinsertion of the pipette 18. The interior of the draw tube 27 is thenaccessible by subsequently inserting pipette 18 coaxially through thepuncturing means.

A wash/alignment module 21 is located at a fixed position on theframework. Its first purpose is to provide vertical basins within whichthe lower end surfaces of pipette 18 can be flushed clean during orafter liquid transfer cycles. It also supports a conductive sensingplate that verifies both the radial alignment and elevational positionof pipette 18 about the pipette axis on the probe arm 17 for monitoringalignment of the pipette. These operations occur at a wash/alignmentstation D along the arcuate path 29 of pipette 18.

A capacitive sensing circuit is operably connected to the pipette 18 andto conductive members located next to the tray 15 and within the sampletube entry port 20. The sensing circuit detects the level of liquid in acontainer on the tray or a draw tube 27 as it is approached by thepipette.

A second analytical means, shown as an Ion Specific Electrode (ISE)module 38 of conventional design and operation, is included within thechemistry instrument 24. It is illustrated generally in FIG. 1.Potentiometric tests may be requested and run by the ISE module 38simultaneously with photometric tests being conducted by the opticalsystem 14.

Samples are delivered to the ISE module 38 by pipette 18 at a sampledelivery station E along the arcuate path 29 (FIG. 3). Module 38 caninclude tests for the presence of a variety of analytes, such as sodium,potassium, chloride, lithium or calcium. For each analyte, all sampletypes are analyzed in the same manner. The different sample types can beloaded using different dilution factors.

The ISE module 38 consists of electrodes specific to the chosen analyte,a reference electrode and the associated fluid system required toprocess tested samples. The potentiometric measurement consists of avoltage difference between the analyte's electrode and the referenceelectrode.

Water is supplied to pipette 18 from a syringe module 22 connected to awater supply container in a container rack 28. The syringe module 22consists of a volume displacement syringe and associated valves leadingto a source of water and a waste water container (not shown). It is usedfor all aspirations of samples, reagents and diluents in the chemistryinstrument 24. The syringe module is of conventional design.

Tubing 23 (FIG. 1) connects syringe module 22 to pipette 18. Tubing 23contains water that can be moved in opposite directions to receive ordischarge liquids at the lower end of pipette 18.

The above components are individually operable under control of adistributed computerized controller system governed by the programmableworkstation 30. Workstation 30 is electronically linked to theinstrument via a bi-directional communications interface. This interfaceis used to communicate patient requisitions to the chemistry instrument24 and to receive the associated test results from the instrument 24.All control functions can be randomly initiated under control ofscheduling software and logic to match pending requisition requirementsand current instrument status conditions.

The external computer can send patient requisitions to the workstationeither individually or in ring segment groups. The workstation can sendtest results to the external computer.

The control system associated with chemistry instrument 24 includesseveral dedicated microprocessors and programmable memory devices. Theyindividually operate the system components as prioritized by schedulingsoftware residing in the instrument CPU board. The workstation 30includes monitoring means for maintaining a current record of the amountof liquid in containers on the sample/reagent tray 15. Controllingsoftware associated with the microprocessors causes the mechanicalcomponents of the chemistry instrument 24 to carry out all operationsefficiently and effectively without operator intervention, using arandom sequence of movements dictated by outstanding test requirements.

The arrangement of operational stations along the arcuate path ofpipette 18 permits transfer of liquids from a draw tube 27 at the sampleaccess station B to a well 36 at a container access station C₁ or C₂ onthe sample/reagent tray or from a well 36 to a cuvette 10 at the cuvetteaccess station A on turntable 11. Alternately, pipette 18 can transfersample diluents (buffers) from the reagent bottles 25 at containeraccess stations C₃ or C₄ on the sample/reagent tray 15 to a well 36 at acontainer access station C₁ or C₂. In addition, it can transfer liquidsfrom one well 36 to another, or from a cup 35 to a well 36 for dilutionpurposes at container access stations C₁ or C₂. Direct transfer ofreagents from bottles 25 to cuvettes 10 can also take place at cuvetteaccess station A. A wash or pipette alignment procedure can also beperiodically accomplished at wash/alignment station D as required. ISEtests are initiated by optional delivery of sample liquids to the ISEstation E.

Sample/Reagent Tray

FIG. 4 illustrates the positional relationship between thesample/reagent tray 15 and the primary components of the chemistryinstrument 24 located about the horizontal platform 238 included withinthe enclosure for the chemistry instrument 24. Details of sample/reagenttray 15 are illustrated in FIGS. 6-9.

FIG. 10 illustrates an area of platform 238 forming a recessed well 240within which the tray 15 is rotatably mounted. Well 240 is centeredabout a fixed vertical support shaft 241 for the tray 15 and includes asurrounding rim 242. The cross-sectional relationships between theseelements is best illustrated in the sectional view shown at FIG. 7.

The illustrated tray 15 is designed to supply reagents to the chemistryinstrument 24 from at least two sizes of conventional reagent bottles25. They are arranged within concentric rings. Additional sizes ofbottles can be accommodated within the tray structure by usingsurrounding adapter sleeves (not shown) that fit properly withinreceiving tray apertures. Bottle labels read by scanners provide bottlesize information and reagent identification data (regent type, lotnumber and bottle serial number) to the chemistry instrument as neededfor monitoring of reagent inventory and life.

The upper end of each reagent bottle 25 is normally covered by aremovable threaded cap (not shown) when manually delivered to thechemistry instrument 24. A "peel and stick" protective cover 239, madefrom a paper or plastic sheet, is utilized across each bottle 25 toprevent contamination and spillage during its usage in the tray 15. Eachcover 239 is slit in an intersecting pattern to facilitate passage ofpipette 18 through it while accessing reagent liquids.

The cylindrical reagent bottles 25 are tilted from vertical to permitthe tip of pipette 18 to penetrate the interior of each bottle to alocation adjacent to the lowermost inclined intersection between thecontainer side and bottom walls. This assures more complete removal ofliquid from within each reagent bottle 25.

The sample/reagent tray 15 is rotated about its central vertical axis byits engagement with a powered driving gear 244 (FIG. 10) that projectsinto well 240. Gear 244 meshes with peripheral gear teeth 243 formedabout the exterior of tray 15. It is operatively powered by steppermotor 16 (FIG. 1).

The circular tray 15 is rotatably mounted on the framework for thechemistry instrument 24 for rotation about a central vertical axisparallel to the axis of the turntable 11. Tray 15 can be indexed to anydesired angular position about its central axis by operation of steppermotor 16.

Typical configurations for the open reagent bottles 25 are illustratedin dashed lines in FIG. 7. As seen in FIGS. 6 and 7, the base of tray 15includes two sets of apertures 132 and 133 suitably sized to receive andsupport at least two sizes of reagent bottles 25. The apertures alsoexpose the bottom of each bottle 25 for optical viewing of bottom labelsapplied to the bottles. In a preferred form of a reagent identificationsystem, circular labels having machine-readable indicia printed on theirsurfaces are scanned from below tray 15 while it is stationary, thuscapturing encoded data pertaining to the bottle contents.

Tray 15 includes a central carrying handle 133. Handle 133 facilitatesremoval of the tray 15 and reagent bottles 25 as a unit, as well as anyattached ring segments 26. A plurality of trays 15 can be interchangedin a chemistry instrument 24 as required for specific test purposes. Theentire tray 15 can also be removed from the chemistry instrument 24overnight and during periods of nonuse. It can then be stored in arefrigerated environment or under other conditions as required by thenature of reagents supplied in the tray.

A series of peripheral posts 134 releasably support separablecircumferential ring segments 26. The ring segments 26 can be attachedto tray 15 while it is located within the chemistry instrument 24enclosure or at a loading station external to the illustrated equipment.

The individual ring segments 26 shown in FIGS. 6, 7 and 9 are eitherprovided with integral molded wells 36 or removable cups 35. The ringsegments 26 are otherwise structurally interchangeable. Each includesradial tabs 135 that fit over the supporting posts 134 when the ringsegments 26 are assembled about the tray 15.

To distinguish the two types of ring segments 26, the outer dependingflanges 253 on the cup ring segments are notched, as shown by notch 254in FIG. 9. The nature of a particular ring segment 26 is determined by alight sensor 252 located on platform 238 immediately adjacent to rim242. The outer upright flanges 253 about the ring segments 26 passbetween the elements of the sensor 252. The relative positions of theseelements is illustrated in dashed lines in the sectional view shown inFIG. 7.

Both cups 35 and wells 36 have identical interior volumes and shapes,the only physical difference between them being that the cups 35 areseparable from a supporting ring segment 26, while the integral wells 36are not. Cups 35 are less densely arranged about the ring segments 26 soas to provide adequate room about them to facilitate manual handling ofthe individual cups as needed.

The functions of cups 35 and wells 36 are designed to be complementaryto one another. Cups 35 can be added to tray 15 individually or as partof a supporting ring segment 26. Wells 36 are always handled as a group.The portable cups 35 are available only to a human operator forintroduction of sample, calibrator, and control liquids. Pipette 18never delivers liquids to cups 35, but can deliver liquids availablewithin cups 35 to cuvettes 10 in turntable 11 as required for assaypurposes. Wells 36 are available only to the chemistry instrument 24.Pipette 18 can use available wells 36 for aliquoting of sample liquid,for dilution of samples before introduction to the ISE module 38, andfor mixing of sample liquid with system diluent or a buffer suppliedfrom a bottle 25 on the sample/reagent tray 15.

Manual access to the sample/reagent tray 15 is available through thehinged tray access cover 8 shown in FIGS. 2 and 3. Access to theindividual ring segments 26 is provided by the segment access port 7.While mechanical interlocks can be provided to restrict opening of cover8 and port 7, they are not essential. Sensors (not shown) are providedto detect their opening and to alert monitoring software residing inworkstation 30 of such events.

Indexing of tray 15 is accomplished by a circular notched indexing ring245 formed at its underside, which moves between an optical sensor 246coupled to workstation 30. A reference "home" angular position of tray15 about the vertical axis of shaft 241 is determined by a projectingindex tab 247 at the bottom of tray 15, which is detected by an opticalsensor 248 within well 240. The relative positions of these elements isalso illustrated in dashed lines in FIG. 7.

A pair of optical scanner ports 250 are located in the base of well 240directly under the two circular paths of reagent bottles 25 supported bytray 15. Scanning devices under the ports 250 are provided to readencoded end labels attached to each reagent bottle 25. Information onthe labels, read through openings under each bottle 25, might relate toreagent identification, lot numbers and reagent aging information.

A line-of-sight optical sensor 256 is arranged across rim 242 forsensing the presence of the removable cups 35 in the ring segments 26.The relative positions of these elements is also illustrated in dashedlines in the sectional view shown in FIG. 7. By combining tray indexinginformation, segment identification information and cup presenceinformation together with liquid transfer data, workstation 30 canmaintain an accurate inventory of the cups 35 and wells 36 available foruse with respect to tests being conducted on the chemistry instrument24.

A conductive metal plate 258 is fixed within well 240 under the circularpaths of the reagent bottles 25. The upper surface of plate 258 isspaced from, but in close proximity to, the exposed bottom surfaces ofthe reagent bottles 25 (FIG. 7). Similarly, a conductive metal plate 260is fixed across the upper surface of rim 242. It includes ribs 261 inclose proximity alongside cups 35 and wells 36 within the ring segments26. Plate 258 is used for capacitive sensing of liquid level within thereagent bottles 25 as liquid within them is approached by the descendingpipette 18. Plate 260 performs the same functions with respect to liquidlevel sensing within cups 35 and wells 36. The liquid level sensingmechanism including these elements is described below.

Reagent Bottle Identification

Machine-readable identifying information is encoded at the bottom ofeach reagent bottle 25 upon a printed label 325 detailed in FIGS. 11 and12. The label can be secured to the circular bottom surface of thereagent bottle 25 by any suitable adhesive system.

Each label 325 preferably has a light surface background on which acontrasting pattern of dots are imprinted. While circular dots areillustrated in FIG. 11, other suitable dot shapes can be used as well.

The label pattern shown in FIG. 11 includes every possible dot locationin the present encoding pattern. It is to be understood that the encodedpattern identifying a specific reagent bottle will display a uniquearrangement of both dots and blank areas where the dots are nowillustrated, the pattern being dependent upon the digital coderepresentative of the encoded data. The code utilized on the labels 325is a multi-bit binary code representing an identification code for aspecific reagent bottle.

Identification label 325 includes a spaced pair of position referencedots 326 and 327 which define and orient a label area. Positionreference dot 326 is a central position dot, designating the approximatecenter of the reagent bottle bottom surface. Position reference dot 327is an orientation dot which is located radially outward from centralposition dot 326 to define a label orientation.

The label area is divided into a plurality of bit fields whose positionsare defined by position reference dots 326 and 327. Each bit field mapsto a single bit of the multi-bit binary bottle identification code. Thebinary value of each bit of the multi-bit binary identification code isdetermined by whether a bit dot 328 is present within the mapped bitfield.

In general, position reference dots 326 and 327 have a minimum area andthe bit dots 328 have a maximum area. The minimum area of positionreference dots 326 and 327 is greater than the maximum area of bit dots328 so that position reference dots 326 and 327 can be easilydistinguished from bit dots 328. In the preferred embodiment, positionreference dots 326 and 327 have a diameter of about 0.054". Bit dots 328have a diameter of about 0.034".

The configuration described above produces a pattern of 45 dots that canbe effectively imprinted within a label area having a diameter of onehalf inch. Position reference dot 326 identifies the center of thepattern. Position reference dot 327 is located at the rim of the patternas an angular index. The label data is encoded by smaller bit dots 328.The bit dots 328 are spaced on approximately 0.1" centers.

The mapping of bit fields to binary code bits is indicated in FIG. 12.The bit dots designated by the digits 0-6 encode seven check bits. Thelabel information is encoded by the bit dots designated by the digits7-43, with dot 7 being the least significant bit. The forty-threeillustrated bit dots 328 provide forty-three bits of binary data, whichis sufficient to encode eleven decimal digits.

A conventional Hamming error detection/correction code can be used toencode the label information. Seven check bits are computed from thedata bits and form a part of the label pattern. When the label is read,the encoding of the check bits allows the detection and correction of anerror in any one of the bit locations about the label 325. Any singlebit may be in error, but the encoded information on the label 325 canstill be recognized correctly. If errors exist at any two bit locations,the existence of an error will be detected, but the information on thelabel cannot be decoded. If errors exist in more than two bits, theresulting information will be unpredictable.

The equipment for reading information encoded on labels 325 isdiagrammatically illustrated in FIG. 13. Each reagent bottle 25 is heldwithin the sample/reagent tray 15 at a location above the horizontalsurface of well 240. Each label 325 can be indexed over one of theoptical scanner ports 250 for label reading purposes. The opticalscanner ports 250 each include a circular filter 330 that blocksentrance of room light while permitting passage of illuminating lightdirected to the label 325 from a location under the port 250.

The information encoded on labels 325 is read by a camera 332 inresponse to reflected light provided by a circumferential ring of lightemitting diodes 334 directed toward the bottom surface of a reagentbottle 25. Camera 332, which is essentially a video camera, includes alens system 335 positioned behind the ring of diodes 334. Lens system335 focuses light from the bottom of reagent bottle 25 onto a receivingscanning matrix 336 of image sensors. In the illustrated example, thematrix 336 has a 192×165 pixel area capable of discriminating betweenthe above-identified dot array.

The camera 132 conveys digital information to controller 312 from whicha digitized image of the bottom of each reagent bottle 25 can be storedin memory. This image can then be electronically "rotated" about thecenter dot 326 and indexed relative to the rim dot 327 to orient bitdots 328 for electronic analysis. The electronic functions required insuch an analysis are believed to be well-known in image-analyzingtechnology today. No further details are necessary in order to enablethose skilled in this area of technology to construct and successfullyuse the described scanning apparatus and associated labels.

The unique labeling scheme described above allows for simple and quickdecoding of reagent bottle identification data. Once the label has beenoriented properly and broken into bit fields, only the presence orabsence of a dot in that bit field need be determined. This is incontrast to many other types of labeling schemes in which indicia sizeor spacing is variable to represent coded information. In the scheme ofthis invention, all bit dot sizes and all spacing between bit dotsremain constant, making for much simpler detection and decoding. Simplethresholding can be used within each bit field to detect whether a dotis present of sufficient area to constitute a bit dot.

Reagent Monitoring

Overview

The purpose of reagent monitoring is to warn the operator when a reagentwithin a particular bottle 25 has been in use too long. Where twochemistry instruments 24 are used in tandem with a common workstation30, each instrument tracks the age and volume of one working bottle foreach reagent defined in its data base. The age of the working bottle ismaintained in the memory of the instrument 24 even when it is removedfrom it for overnight storage of other purposes.

This description pertains to the manner by which the chemistryinstrument 24 manages the sample/reagent tray 15. It describes the wayin which the working bottles 25 of reagent and the working lifetimes oftheir reagent contents are tracked, how the instrument decides when anew bottle is to be used, and how reagent lot number changes arehandled. It describes how the system reacts when the tray access cover 8is opened. It further describes the activities of the system when areagent bottle 25 is found to contain less reagent than is required fora requisitioned assay.

The chemistry instrument 24 shown in the drawings includes asample/reagent tray 15 having room for forty reagent bottles 25. As oneexample, these might be twenty large (30 ml) bottles and twenty small(12 ml) ones. The tray 15 can be accessed by manually opening the hingedtray access cover 8. Cover 8 is provided with a sensor so that thecontroller system will be provided with a signal indicating whenever thereagent bottles 25 might have been disturbed.

Sample/reagent tray controller 312 will operate the motor 16 and theelectronics associated with optical scanner ports 250 to read the labelsat the bottom of every reagent bottle 25 at the conclusion of anyoperation requiring tray access cover 8 to have been opened. Thisinformation is used by the software to update stored data pertaining totheir reagent identifications, lot codes, and serial numbers.

The volume in each reagent bottle 25 accessed by pipette 18 is measuredeach time that the instrument uses a reagent. This is done by using thepipette's fluid sensing capability to detect the elevation of liquid,which is then related to the interior volume of the bottle by usingstored information relating to the bottle size.

The logic system associated with sample/reagent tray 15 supports a modeof operation wherein two bottles 25 of each reagent can be on the tray15 at any given time. When the working bottle 25 is emptied, theinstrument 24 will then start loading from the reserve bottle.

Any secondary or non-working bottles of reagents are also timed while inthe tray 15. However, since they are not in use, their respective liquidvolumes are not tracked. They are tracked by their positions within tray15 only. Their age is not maintained in the instrument's memory if theyare removed. It is possible to remove the tray 15 after the instrument24 has been turned off and subsequently replace it before powering upthe instrument 24 again. In this case, all of the bottles' ages will bemaintained in memory.

Once introduced into the chemistry instrument 24, the contents of aprimary reagent bottle 25 will continue to be used by it until thebottle is empty or is removed by an operator. When a bottle 25containing reagent is first introduced into the chemistry instrument 24in the tray 15, the controlling logic will assume it to be freshlyreconstituted. A working expiration time will be established for it atsuch introduction. The number of hours remaining before expiration isavailable for display as needed on the monitor 31. If a reagent bottle25 remains in the system beyond this time, the operator will be warnedby an appropriate display message and the contents of the bottle will be"marked" as being expired on a status screen.

Reagent Definition Data Base

A reagent definition data base resides in disk memory provided withworkstation 30 in the form of a shared data file (information common totwo chemistry instruments 24) and one or more instrument-specific datafiles.

The shared data file defines the characteristics of each reagent. Thisincludes the name, bottle identification, fluid type and workinglifetime. The data pertaining to working lifetime is set up by theoperator. The working lifetime is defined as the length of time duringwhich the reagent within a bottle 25 is considered functionally usablefrom the time a new bottle is opened or reconstituted. The bottleidentification is a number encoded into a machine-readable bottle label.The identification data captured by the bottle label scanning equipmentalso encodes the size and shape of the bottles. Ranges of identificationvalues are reserved for particular bottle types. Captured informationpertaining to fluid type is used by the operator interface inworkstation 30 to generate appropriate choice lists.

The instrument-specific data base stores the status of each workingreagent bottle 25, including working lot number, serial number,expiration time and volume. This data is stored in a non-volatilefashion so as to maintain data concerning each working reagent bottleeven when it has been removed from the system or during periods whenpower has been lost. The volume remaining in each working reagent bottleis updated each time the bottle is used.

Sample/Reagent Tray Status Data

Each instrument CPU board maintains the data pertaining to the status ofthe bottles 25 in each tray position in non-volatile random accessmemory. For each position in the tray, the system stores the type ofreagent as well as its lot code and serial number, plus the volume,working expiration time and status of the container in question. Aspecial software flag is set when the tray access cover 8 is opened orafter power interruption, and cleared when the label on each bottle 25within tray 15 is subsequently read by the scanning devices underoptical scanner ports 250. When it is set, the prior data concerning thebottles is not totally invalid, since it represents the state of thebottle before the event.

Data is maintained in the instrument 24 as to whether or not eachreagent is required by waiting, on-hold and active instrument workload.This is maintained by a background status update task in the instrumentCPU board, so that it is continually updated. This data is used by thereagent status screen to show which reagents are required by theworkload. This can also be used by an operator to do requirementschecking through workstation 30 to warn for insufficient reagent.

Fluid Transfers From Reagent Bottles

Fluid transfers involving reagent bottles 25 are always done fromworking or primary bottles of a reagent. The working bottle isrecognized by its label information. The system supports having multiplebottles of each reagent, one designated by the instrument as a workingbottle and the others as reserve bottles. When the working bottlebecomes empty a reserve bottle becomes the new working bottle.

Proper operation of the chemistry instrument 24 does not permit liquidto be added to a working bottle. A bottle will be rejected if its liquidvolume has increased above a specified minimum amount since it was lastaccessed by probe 18. It is assumed that an operator might open thecover, pour some of the working reagent from a particular reagent bottle25, and then return the reagent bottle to sample/reagent tray 15. Suchactivity can be accommodated by the controlling software, since it ispresumed that removal of liquid from a reagent bottle 25 will notcontaminate its content, whereas addition of liquid to it will.

Every time a liquid transfer is to be made from a bottle 25, the workingbottle must be identified or selected from a set of reserve bottles.When the transfer is started, a liquid transfer module controller isprovided with data containing limits within which the volume in theappropriate working bottle should be found. If the liquid transfermodule controller finds the volume within the identified reagent bottle25 to be short or outside the limits, it aborts the transfer, discardsany received liquid in the pipette 18 and communicates data relating tothe measured volume to the instrument CPU board.

If no working bottle for a needed reagent can be identified by thesoftware, a new working bottle must be selected. The reserve bottles ofreagent are each marked in memory with a time of appearance on the tray15. The oldest reserve bottle then becomes the next working bottle. Ifmore than one reserve bottle is marked in memory with the same time ofappearance, the one with the lowest numbered tray position will bearbitrarily selected.

The above rules are only followed for the lot number currently in use.If more than one lot of reagent is present, the working reagent bottle25 will be chosen from the bottles of the working lot number. Allbottles of other lots are considered reserve bottles.

The capacitive sensing system for detecting fluid levels within theinstrument 24 is utilized to capture reagent volume information for eachworking bottle of reagent on a real-time basis during all operations. Aspipette 18 is lowered into a reagent bottle 25, it is stopped byoperation of the liquid transfer module controller when the liquidsurface within the bottle is sensed. The liquid transfer modulecontroller has data relating to the bottle identification, which impliesthe bottle's diameter and dead volume. The volume of reagent within thebottle 25 is then deduced by the liquid transfer module controller fromthe height of the pipette tip.

Each time a reagent bottle 25 is probed by pipette 18, the stored datarelating to the volume of reagent remaining within it is verified andupdated, if necessary. The liquid transfer module controllercommunicates data with respect to the volume of reagent in the reagentbottle 25 back to the instrument CPU board in microliters, excluding thedead volume. If a transfer was performed from the reagent bottle 25, thereported volume is corrected for the volume of reagent removed.

The instrument CPU board is also programmed to respond to unexpectedvolumes of reagent measured by the probing action of pipette 18. When afluid transfer from a reagent bottle 25 is performed, the liquidtransfer module controller calculates the high and low limits to theacceptable volume that should be within the selected bottle. Thesoftware allows for a predetermined volume measurement error tolerance.If the tray access cover 8 has not been opened since the last time thatthe selected bottle 25 was probed, the volume of reagent within itshould not deviate from the last-measured volume by more than thetolerance in either direction. If it does, this is reported as a warningto the operator. The operator's normal course of action in this case isto go to diagnostics.

If the tray access cover 8 has been opened since the last time theselected working reagent bottle 25 was probed, the instrument 24 willexpect the volume of reagent within each reagent bottle 25 to be betweenthe last volume (plus tolerance) and zero. If the measured volume ofreagent within a probed bottle 25 is found to be too great, use of thebottle is not allowed. This guards against use of bottle contents thatmight have been accidently or purposefully contaminated or dilutedduring their use in the instrument.

The instrument 24 is programmed to respond to data indicating that thevolume of reagent in a working bottle is short of that required for arequisitioned assay or test. Each time that such a reagent bottle 25 isprobed, the liquid transfer module controller will report that itsliquid content is empty. This is reported to the operator by a messageon monitor 31.

If a reagent bottle 25 is found short during a fluid transfer, thecontents of the probe are discarded, and the run being loaded iscanceled. If other reagent bottles 25 of this type are on the tray, anew working bottle is selected and the run is rescheduled. Otherwise,the run is put on hold.

When the instrument CPU board is re-initialized, it assumes that powerhas been removed from the chemistry instrument 24. Since the tray accesscover 8 might have been opened while power was removed, the systembehaves as if the cover 8 has been opened. The instrument CPU board iscapable of continuing to monitor the sensors that detect opening ofcover 8 while carrying out diagnostic procedures, so the tray 15 is onlyscanned as necessary after diagnostics.

Every time the cover 8 has been opened, each reagent bottle 25 is markedin the controlling software as requiring reading of its label. Thiscauses the bottle label to be read. When the cover 8 is again closed,the system scans the sample/reagent tray 15 to read all the bottlelabels. The system remembers the tray status in memory until the newstatus is figured out completely. Thus, if the system is reset during ascan, the previous data is not lost. If power is lost while a new statusis being written, the system starts a new scan.

When a reagent bottle 25 is recognized as a new working bottle, theworking bottle expiration time is updated in the reagent data base. If atest uses an external reagent blank, a new blank value is stored when anew bottle is started for any reagent involved in the test's loadsequence. The scheduling software within the instrument CPU board willthen load an external reagent blank cuvette for the first run ofturntable 11 scheduled using the new reagent bottle 25.

If a patient or quality control test run is being loaded onto theturntable 11 and an external reagent blank has been loaded from aworking reagent bottle, but a new bottle is started before the reactioncuvette for the test has been loaded, the test run must be rescheduledby the controlling software. Both the external reagent blank and thereaction cuvette must be loaded using reagent from the same reagentbottle 25.

Bottles 25 containing reagent of a lot other than the working lot areignored until the system has no choice but to pick a new working reagentfrom them. A new working reagent is then selected from them by using theoldest appearance time or the lowest tray position, if the times areequal.

The system requires a test to be calibrated before running a patient orquality control test from a new lot. When a new working reagent must beselected, and all of the choices are from a new lot, the test is markedas requiring calibration. If a calibration request is waiting, a workingbottle is selected and the calibration is scheduled.

The invention has been described in language more or less specific as tostructural features. It is to be understood, however, that the inventionis not limited to the specific features shown, since the means andconstruction herein disclosed comprise a preferred form of putting theinvention into effect. The invention is, therefore, claimed in any ofits forms or modifications within the proper scope of the appendedclaims appropriately interpreted to include appropriate equivalents.

We claim:
 1. A method of labeling a reagent bottle with a bottleidentification code for subsequent reading of the bottle identificationcode by an automated chemical analyzer, the method comprising thefollowing steps:locating a spaced pair of position reference dots withinan imprinted pattern of dots on a label to define and orient a labelarea by imprinting a central position dot at the approximate center ofthe label area and imprinting an orientation dot at the rim of thepattern at a location spaced radially outward from the central positiondot; dividing the remainder of the label area into a plurality of bitfields, the positions of the bit fields surrounding being defined by thespaced pair of position reference dots, the spacing between theimprinted pair of reference dots being substantially greater than thespacing between adjacent bit fields about the label area and also beinggreater than the spacing between each of the imprinted reference dotsand the bit fields adjacent to it; generating a multi-bit binary bottleidentification code; mapping each bit field to a single bit of themulti-bit binary bottle identification code; and imprinting bit dotswithin selected bit fields about the label area, the location of eachimprinted bit dot being dependent upon the binary value of the mappedbit field of the multi-bit binary bottle identification code; theimprinted position reference dots having a minimum area and theimprinted bit dots having a maximum area, the minimum area of theimprinted position reference dots being greater than the maximum area ofthe imprinted bit dots, the imprinted position reference dots beingdistinguishable from the imprinted bit dots by their relatively greaterareas and spacing.
 2. An identification label for use on the bottomsurface of a reagent bottle having a bottle identification code forsubsequent reading of the bottle identification code by an automatedchemical analyzer, comprising:a label having a surface background onwhich a contrasting pattern of dots is imprinted; the pattern of dotsincluding a spaced pair of imprinted position reference dots in the formof a central position dot located at the approximate center of the labeland an orientation dot spaced radially outward from the central positiondot at the rim of the pattern, the central position dot and orientationdot defining and orienting a label area containing both of them: theremaining label area being divided into a plurality of bit fields withthe positions of the bit fields surrounding and being defined by thespaced pair of position reference dots, the spacing between theimprinted pair of reference dots being substantially greater than thespacing between adjacent bit fields about the label area and also beinggreater than the spacing between each of the imprinted reference dotsand the bit fields adjacent to it; and bit dots imprinted in selectedbit fields about the label area; the imprinted position reference dotshaving a minimum area and the imprinted bit dots having a maximum area,the minimum area of the imprinted position reference dots being greaterthan the maximum area of the imprinted bit dots, the imprinted positionreference dots being distinguishable from the imprinted bit dots bytheir relatively greater areas and spacing; wherein each bit field mapsto a single bit of a multi-bit binary bottle identification code, thebinary value of each bit of the multi-bit binary identification codedetermining whether a bit dot is present in the mapped bit field.
 3. Incombination with the label of claim 2:a reagent bottle including abottom surface, the imprinted label being affixed to the bottom surfaceof the reagent bottle.